The non-pregnant uterus has been shown to be an effective immunization site, leading to strong serum antibody responses after challenge of the female host. Yet the uterus can also serve as an extremely successful natural graft site for the developing allogeneic fetus. The mechanism(s) which enable this dichotomy of function will be examined in the proposed study. One means which will be used to investigate this question is comparison of immune responses generated against hapten-protein conjugate antigens placed in the uterine lumina of virgin, pseudopregnant, and pregnant animals. Such experiments will demonstrate how the female's immune capacity is affected by the hormonal state of pregnancy alone (produced by the pseudopregnant state) and under the influence of the intact mechanisms of maternal/fetal interaction. In addition, the proposed project will study the local, secretory immune component of sensitization across the intact uterine mucosa. This will be accomplished by determining IgA levels (both total and antigen-specific) produced in serum and uterine fluids after in vivo immunization and challenge. Also, lymphoid cells from various organs and explants of uterine tissue from intrauterine-immunized hosts will be challenged with antigen under in vitro culture conditions to determine the quantity and location of specific antibody-forming cells, especially those producing IgA. These studies will help to clarify the dual role of the uterus as an immunization site capable of protecting the female from exogenous infectious agents and as a transplantation site for the attachment and maintenance of the fetal allograft until parturition.